Evidence indicates that distress intolerance, or one's inability to persist in goal directed activity while experiencing affective distress, provides a behavioral proxy of avoidance of affective distress, and is indicative of the ability to remain abstinent and in treatment during the early stages of an abstinence attempt. Despite the utility of the behavioral measures of distress intolerance in identifying individuals at risk for poor substance use outcomes, this line of work has yet to be utilized in an assessment paradigm capable of identifying the neural processes associated with distress intolerance. Although previous studies have identified key neural structures implicated in the relapse process including prefrontal and limbic regions, none to date have integrated these areas in an assessment paradigm that captures one's ability to tolerate distress without engaging in avoidance behavior. The specific aims of this study will thus allow for the bridging of scientists within affective and cognitive neuroscience with clinical and behavioral psychology in the utilization of a well validated distress intolerance paradigm in fMRI to identify key neurobiological indices responsible for distress intolerance. The distress intolerance paradigm provides an empirically validated and innovative approach to this line of research because it (1) elicits real-time distress in the context of goal directed activity as opposed to recalling a previously distressing event or viewing distressing pictures, (2) has repeatedly demonstrated a relationship with a number of "real-world" substance abuse outcomes, and perhaps most importantly, (3) allows for the study of one's behavioral response to distress (i.e. quitting the task) during the experimental procedure. Specifically, the primary aims of the current application are to identify the neural processes associated with the avoidance of affective distress (i.e., distress intolerance) in a sample of 30 healthy non-drug using and 30 cocaine dependent adults entering residential substance abuse treatment (Total n = 60), and the influence of these neural processes in explaining the relationship between distress intolerance and cocaine dependence. PUBLIC HEALTH RELEVANCE: Distress intolerance (i.e., the avoidance of affective distress) is associated with increased rates of substance dependence, relapse to substance use, as well as incidence of DSM-IV borderline personality disorder, antisocial personality disorder, and bulimia nervosa. Thus, identifying the neural mechanisms underlying distress intolerance will aide in the development of appropriate prevention and intervention programs and therefore holds considerable public health significance. The primary aims of the current application are to identify the neural processes associated with distress intolerance in a sample of 30 healthy non-drug using and 30 cocaine dependent adults entering residential substance abuse treatment (total n = 60), as well as the influence of these neural processes on explaining the relationship between distress intolerance and cocaine dependence.